Management Of Stroke Health Article

Thrombolysis is likely to be beneficial in patients with major ischaemic stroke with a large ischaemic penumbra (Figure 2), but is likely to be ineffective or harmful in completed infarction and when the ischaemic penumbra is small.

• In a randomized controlled trial of recombinant tissue plasminogen activator (rt-PA) given within 3 hours, thrombolysis significantly improved outcome despite an increased risk of cerebral haemorrhage. ² The improved outcome in the thrombolysis group was maintained at 1 year.

• Systematic reviews of intravenous thrombolytic therapy suggest benefit from thrombolysis within the first 6 hours of stroke, with a significant reduction in combined death or dependency at the end of follow-up despite an increase in the number of intracranial haemorrhages and deaths. Patients treated within 3 hours exhibited improved outcome with no excess deaths.

• A recent re-analysis of individual patient data from the NINDS, ECASS I and II, and ATLANTIS trials (99% of patients randomized in trials of rt-PA in stroke) has confirmed that the benefit from thrombolysis decreases with time since stroke onset ( Figure 4). ³ It is most beneficial if given within 90 minutes.

Current guidelines regarding thrombolysis vary, but there is agreement that it should be administered only by a physician with expertise in stroke and should be avoided more than 3 hours after stroke onset except as part of a randomized trial.

Intra-arterial thrombolysis enables treatment of vessel occlusion and may allow safer treatment of patients at increased risk of haemorrhagic complications. One randomized trial showed benefit in proximal middle cerebral artery occlusion. There are no trials in the posterior circulation (e.g. basilar artery occlusion) or direct comparisons between intra-arterial and intravenous thrombolysis.

Antiplatelet therapy –aspirin started within 48 hours of acute ischaemic stroke onset reduces mortality and recurrent stroke, so early brain imaging to exclude haemorrhage is important. Patients intolerant of aspirin should be treated with clopidogrel or dipyridamole. There is no clear evidence favouring any particular dose of aspirin, but lower doses are preferred because toxicity is dose-related. Current guidelines suggest 150–300 mg daily initially, followed by long-term treatment with 75–150 mg daily. The use of combination antiplatelet therapy is discussed in the Secondary prevention section.

Heparins and heparinoids –immediate therapy with systemic anticoagulants (including unfractionated heparin, low molecular weight heparin, heparinoids and specific thrombin inhibitors) in patients with acute ischaemic stroke is not associated with benefit. These agents reduce the risk of DVT and pulmonary embolus, but are associated with a significant and dose-dependent risk of intracranial haemorrhage. There is little evidence to guide the treatment of specific causes of ischaemic stroke such as dissection and basilar artery thrombosis – conditions that are associated with progressive symptoms.

Oral anticoagulants –patients in atrial fibrillation after presumed ischaemic stroke or TIA should be anticoagulated to prevent further stroke. The best time to start therapy after ischaemic stroke is unclear, however, because the risk of haemorrhagic transformation is difficult to predict. Current guidelines suggest that patients should be treated with aspirin for the first 2 weeks before anticoagulation is introduced.

Other therapies –there is insufficient evidence to support the use of fibrinogen-depleting agents, corticosteroids and haemo-dilution in acute ischaemic stroke. Neuroprotective agents have attracted interest, but results have been disappointing.

Coagulation defects in patients with intracerebral haemorrhage should be corrected urgently. In a recent phase II trial, recombinant activated factor VII reduced haematoma expansion, mortality and disability when given within 4 hours of stroke onset and a phase III (FAST) trial is now in progress.

Surgical evacuation of medium-sized intracerebral haematomas was not shown to be beneficial in the recent STICH trial but patients with lobar haemorrhages, substantial mass effect or rapidly deteriorating condition should be discussed with the neurosurgeons. Patients with cerebellar stroke (particularly those with acute hydrocephalus from compression of the aqueduct) should be referred urgently to a neurosurgeon for possible ventricular shunting and decompression surgery.